Single-nucleotide polymorphisms and mRNA expression of influence treatment response in triple negative breast cancer patients undergoing chemotherapy.

Triple negative breast cancer (TNBC) is typically associated with poor and interindividual variability in treatment response. Cytochrome P450 family 1 subfamily B1 () is a metabolizing enzyme, involved in the biotransformation of xenobiotics and anticancer drugs. We hypothesized that, single-nucleotide polymorphisms (SNPs), 142 C>G, 4326 C>G and 4360 A>G, and mRNA expression might be potential biomarkers for prediction of treatment response in TNBC patients. SNPs genotyping (76 TNBC patients) was performed using allele-specific polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism methods and mRNA expression of (41 formalin-fixed paraffin embeddedblocks) was quantified using quantitative reverse transcription PCR. Homozygous variant genotype (GG) and variant allele (G) of 4326C>G polymorphism showed significantly higher risk for development of resistance to chemotherapy with adjusted odds ratio (OR): 6.802 and 3.010, respectively. Whereas, 142 CG heterozygous genotype showed significant association with goodtreatment response with adjusted OR: 0.199. 142C-4326G haplotype was associated with higher risk for chemoresistance with OR: 2.579. Expression analysis revealed that the relative expression of was downregulated (0.592) in cancerous tissue compared with normal adjacent tissues. When analysed for association with chemotherapy response, expression was found to be significantly upregulated (3.256) in cancerous tissues of patients who did not respond as opposed to those of patients who showed response to chemotherapy. Our findings suggest that SNPs together with mRNA expression of may be useful biomarkers to predict chemotherapy response in TNBC patients.